Sex reversal and comparative data undermine the W chromosome and support Z-linked DMRT1 as the regulator of gonadal Sex differentiation in birds

Hirst, Claire E., Major, Andrew T., Ayers, Katie L., Brown, Rosie J., Mariette, Mylene, Sackton, Timothy B. and Smith, Craig A. 2017, Sex reversal and comparative data undermine the W chromosome and support Z-linked DMRT1 as the regulator of gonadal Sex differentiation in birds, Endocrinology, vol. 158, no. 9, pp. 2970-2987, doi: 10.1210/en.2017-00316.

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Title Sex reversal and comparative data undermine the W chromosome and support Z-linked DMRT1 as the regulator of gonadal Sex differentiation in birds
Author(s) Hirst, Claire E.
Major, Andrew T.
Ayers, Katie L.
Brown, Rosie J.
Mariette, MyleneORCID iD for Mariette, Mylene
Sackton, Timothy B.
Smith, Craig A.
Journal name Endocrinology
Volume number 158
Issue number 9
Start page 2970
End page 2987
Total pages 18
Publisher Oxford University Press
Place of publication Cary, N.C.
Publication date 2017-09-01
ISSN 0013-7227
Keyword(s) Animals
Chick Embryo
Embryonic Development
Gene Expression Regulation, Developmental
Sex Chromosomes
Sex Determination Processes
Sex Differentiation
Transcription Factors
Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
Summary The exact genetic mechanism regulating avian gonadal sex differentiation has not been completely resolved. The most likely scenario involves a dosage mechanism, whereby the Z-linked DMRT1 gene triggers testis development. However, the possibility still exists that the female-specific W chromosome may harbor an ovarian determining factor. In this study, we provide evidence that the universal gene regulating gonadal sex differentiation in birds is Z-linked DMRT1 and not a W-linked (ovarian) factor. Three candidate W-linked ovarian determinants are HINTW, female-expressed transcript 1 (FET1), and female-associated factor (FAF). To test the association of these genes with ovarian differentiation in the chicken, we examined their expression following experimentally induced female-to-male sex reversal using the aromatase inhibitor fadrozole (FAD). Administration of FAD on day 3 of embryogenesis induced a significant loss of aromatase enzyme activity in female gonads and masculinization. However, expression levels of HINTW, FAF, and FET1 were unaltered after experimental masculinization. Furthermore, comparative analysis showed that FAF and FET1 expression could not be detected in zebra finch gonads. Additionally, an antibody raised against the predicted HINTW protein failed to detect it endogenously. These data do not support a universal role for these genes or for the W sex chromosome in ovarian development in birds. We found that DMRT1 (but not the recently identified Z-linked HEMGN gene) is male upregulated in embryonic zebra finch and emu gonads, as in the chicken. As chicken, zebra finch, and emu exemplify the major evolutionary clades of birds, we propose that Z-linked DMRT1, and not the W sex chromosome, regulates gonadal sex differentiation in birds.
Language eng
DOI 10.1210/en.2017-00316
Field of Research 070206 Animal Reproduction
060803 Animal Developmental and Reproductive Biology
060899 Zoology not elsewhere classified
07 Agricultural And Veterinary Sciences
11 Medical And Health Sciences
06 Biological Sciences
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2017, Endocrine Society
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